Friday, 19 December 2014

Uric acid and bipolar disorder

Bipolar disorder appearing again on this blog this week? It's just the way that the papers fall...

With a title like: 'Increased uric acid levels in bipolar disorder subjects during different phases of illness' I was hardly likely to pass up the opportunity to discuss the paper by Umberto Albert and colleagues [1] and their suggestion that there may be a lot more to see when it comes to "a purinergic dysfunction associated with BD [bipolar disorder]".
I lost the defuser gun when I misplaced the invisible car.

Based on the analysis of serum uric acid (UA) levels in 150 participants formally diagnosed with BD compared with "150 age- and gender-matched subjects with MDD [major depressive disorder], OCD [obsessive compulsive disorder], or Schizophrenia", researchers reported that: "Mean serum UA levels (5.06±1.45 vs. 4.17±1.05mg/dL) and rates of hyperuricaemia (30.7% vs. 6.7%) were significantly higher in the bipolar than in the control group." The authors pointed out the limitations of their study: "Our study suffers from the lack of a healthy comparison group; moreover, longitudinal data are missing" so no need for me to say anything further in that respect.

Uric acid, more commonly associated with a condition like gout, has been getting quite a bit of research attention when it comes to behaviour and psychiatry down the years. I've talked previously on this blog about the intriguing work suggestive of a possible connection between levels of uric acid and impulsivity (see here) highlighting a possible biology - trait connection. As per the Albert findings - "No differences were detected between bipolars in different phases of illness, with all three groups (manic, depressive and euthymic bipolars) showing significantly higher UA levels as compared to controls" - other research has hinted that the relationship between uric acid and BD is quite a bit more than just one related to trait [2]. I'm open to accepting that this might however change as more research is done on this topic.

Mechanism of effect for uric acid in BD? A very good question. Unfortunately I don't have a good answer at the moment, aside from reiterating the Albert suggestion "of a purinergic dysfunction associated with BD". Going all the way back to the 1921 book by Emil Kraeplin where the connection between uric acid and "manic symptoms" was discussed, there is quite a long history attached to this area. Even further back, the paper by Sutherland (1892) [3] talked about uric acid diathesis in children exemplified by: "keen precocious minds, and small restless bodies; they are excitable, nervous, bright and amusing at one time, and greatly depressed at another". Lithium salts were the treatment of choice for the 'gouty diseases' [4] and perhaps might offer some further explanation for the mechanism of effect in BD.

Other than that I can say no more, aside from pointing out that if one considers uric acid to be an agent of inflammation [5] and associated with other inflammatory responses [6], one might entertain some possible association between elevated levels of the stuff and other potentially important work in the area of BD...

And to close: White Coats by Foxes.


[1] Albert U. et al. Increased uric acid levels in bipolar disorder subjects during different phases of illness. J Affect Disord. 2014 Nov 15;173C:170-175.

[2] Kesebir S. et al. Increased uric acid levels in bipolar disorder: is it trait or state? J Biol Regul Homeost Agents. 2013 Oct-Dec;27(4):981-8.

[3] Sutherland GA. On some Symptoms Associated with the Uric Acid Diathesis in Children. Br Med J. 1892 Apr 23;1(1634):856-8.

[4] Amdisen A. & Hildebrandt J. Use of lithium in the medically ill. Psychother Psychosom. 1988;49(2):103-19.

[5] Shi Y. Caught red-handed: uric acid is an agent of inflammation. The Journal of Clinical Investigation 2010;120(6):1809-1811. doi:10.1172/JCI43132.

[6] Lyngdoh T. et al. Elevated serum uric acid is associated with high circulating inflammatory cytokines in the population-based Colaus study. PLoS One. 2011;6(5):e19901.

---------- Albert U, De Cori D, Aguglia A, Barbaro F, Bogetto F, & Maina G (2014). Increased uric acid levels in bipolar disorder subjects during different phases of illness. Journal of affective disorders, 173C, 170-175 PMID: 25462413